Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Eviplera

Eviplera 200 mg/25 mg/245 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 19

HOS-214419 · Präparat HOS-155326

The combination of Eviplera and dabigatran etexilate should be used with caution. IMMUNOSUPPRESSANTS Tacrolimus/Tenofovir disoproxil/ Tacrolimus: No dose adjustment is required. Emtricitabine AUC: ↔ Cmax: ↔ Cmin: N/A

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): tacrolimus (HOS-085202) dabigatran etexilate (HOS-086233)

Wechselwirkungen · Eviplera

Eviplera 200 mg/25 mg/245 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 19

HOS-214420 · Präparat HOS-155326

Emtricitabine: AUC: ↔ Cmax: ↔ Cmin: N/A

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Wechselwirkungen · Eviplera

Eviplera 200 mg/25 mg/245 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 19

HOS-214421 · Präparat HOS-155326

Tenofovir: AUC: ↔ Cmax: ↔ Cmin: N/A ANTIDIABETICS Metformin/Emtricitabine Interaction not studied. No dose adjustment is required. Metformin (850 mg single dose)/ Metformin: Rilpivirine AUC: ↔ Cmin: N/A Cmax: ↔ Metformin/Tenofovir disoproxil Interaction not studied. HERBAL PRODUCTS St. John’s wort Interaction not studied with any of Eviplera must not be used in (Hypericum perforatum) the components of Eviplera. combination with products containing St. John’s wort as co- administration may cause significant decreases in rilpivirine plasma concentrations. This may result in loss of therapeutic effect of Eviplera (see section 4.3).

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): tenofovir (HOS-088083) metformin (HOS-091032)

Wechselwirkungen · Eviplera

Eviplera 200 mg/25 mg/245 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 19–20

HOS-214422 · Präparat HOS-155326

19  Medicinal product by therapeutic Effects on medicinal product Recommendation concerning areas levels. co-administration with Eviplera Mean percent change in AUC, Cmax, Cmin HMG CO-A REDUCTASE INHIBITORS Atorvastatin/Emtricitabine Interaction not studied. No dose adjustment is required. Atorvastatin (40 mg once daily)/ Atorvastatin: Rilpivirine1 AUC: ↔ Cmin: ↓ 15% Cmax: ↑ 35%

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): atorvastatin (HOS-086304)

Wechselwirkungen · Eviplera

Eviplera 200 mg/25 mg/245 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 20

HOS-214423 · Präparat HOS-155326

Rilpivirine: AUC: ↔ Cmin: ↔ Cmax: ↓ 9% Atorvastatin/Tenofovir disoproxil Interaction not studied. PHOSPHODIESTERASE TYPE 5 (PDE-5) INHIBITORS Sildenafil/Emtricitabine Interaction not studied. No dose adjustment is required. Sildenafil (50 mg single dose)/ Sildenafil: Rilpivirine1 AUC: ↔ Cmin: N/A Cmax: ↔

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): atorvastatin (HOS-086304) sildenafil (HOS-086162)

Wechselwirkungen · Eviplera

Eviplera 200 mg/25 mg/245 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 20

HOS-214424 · Präparat HOS-155326

Rilpivirine: AUC: ↔ Vardenafil2 Cmin: ↔ Tadalafil2 Cmax: ↔ Sildenafil/Tenofovir disoproxil Interaction not studied. N/A = not applicable 1 This interaction study has been performed with a dose higher than the recommended dose for rilpivirine hydrochloride assessing the maximal effect on the co-administered medicinal product. The dosing recommendation is applicable to the recommended dose of rilpivirine of 25 mg once daily. 2 These are medicinal products within class where similar interactions could be predicted. 3 This interaction study has been performed with a dose higher than the recommended dose for rilpivirine hydrochloride assessing the maximal effect on the co-administered medicinal product. 4 The predominant circulating metabolite of sofosbuvir. 5 Study conducted with additional voxilaprevir 100 mg to achieve voxilaprevir exposures expected in hepatitis C virus (HCV) infected patients. 6 Study conducted with emtricitabine/rilpivirine/tenofovir alafenamide fixed-dose combination tablet.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): sofosbuvir (HOS-108928) tenofovir alafenamide (HOS-110476) hepatitis C virus (HOS-108813) voxilaprevir (HOS-108930) sildenafil (HOS-086162)

Nebenwirkungen · Eviplera

Eviplera 200 mg/25 mg/245 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 21

HOS-214425 · Präparat HOS-155326

Summary of the safety profile

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Nebenwirkungen · Eviplera

Eviplera 200 mg/25 mg/245 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 21

HOS-214426 · Präparat HOS-155326

The combination of emtricitabine, rilpivirine and tenofovir disoproxil has been studied as the component products in treatment-naïve patients (Phase III studies C209 and C215). The single-tablet regimen (STR), Eviplera, has been studied in virologically suppressed patients who switched from a regimen containing a ritonavir-boosted PI (Phase III study GS-US-264-0106) or from efavirenz/emtricitabine/tenofovir disoproxil (Phase IIb study GS-US-264-0111). In treatment-naïve patients, the most frequently reported adverse reactions considered possibly or probably related to rilpivirine hydrochloride and emtricitabine/tenofovir disoproxil were nausea (9%), dizziness (8%), abnormal dreams (8%), headache (6%), diarrhoea (5%) and insomnia (5%) (pooled data from the Phase III clinical studies C209 and C215, see section 5.1). In virologically suppressed patients switching to Eviplera, the most frequently reported adverse reactions considered possibly or probably related to Eviplera were fatigue (3%), diarrhoea (3%), nausea (2%) and insomnia (2%) (48 week data from the Phase III study GS-US-264-0106). The safety profile of emtricitabine and tenofovir disoproxil in these studies was consistent with the previous experience with these agents when each was administered with other antiretroviral agents.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Eviplera

Eviplera 200 mg/25 mg/245 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 21

HOS-214427 · Präparat HOS-155326

In patients receiving tenofovir disoproxil, rare events of renal impairment, renal failure and uncommon events of proximal renal tubulopathy (including Fanconi syndrome) sometimes leading to bone abnormalities (infrequently contributing to fractures) have been reported. Monitoring of renal function is recommended for patients receiving Eviplera (see section 4.4).

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Nebenwirkungen · Eviplera

Eviplera 200 mg/25 mg/245 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 21

HOS-214428 · Präparat HOS-155326

Discontinuation of Eviplera therapy in patients co-infected with HIV and HBV may be associated with severe acute exacerbations of hepatitis (see section 4.4).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Eviplera

Eviplera 200 mg/25 mg/245 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 21

HOS-214429 · Präparat HOS-155326

Tabulated summary of adverse reactions

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Nebenwirkungen · Eviplera

Eviplera 200 mg/25 mg/245 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 21

HOS-214430 · Präparat HOS-155326

The adverse reactions considered at least possibly related to treatment with the components of Eviplera from clinical study and post-marketing experience are listed in Table 2, below, by body system organ class and frequency. Within each frequency grouping, undesirable effects are presented

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Eviplera

Eviplera 200 mg/25 mg/245 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 21–22

HOS-214431 · Präparat HOS-155326

21 in order of decreasing seriousness. Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100) or rare (≥ 1/10,000 to < 1/1,000).

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Nebenwirkungen · Eviplera

Eviplera 200 mg/25 mg/245 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 22

HOS-214432 · Präparat HOS-155326

Table 2: Tabulated summary of adverse reactions to Eviplera based on clinical study and post-marketing experience with Eviplera and its individual components

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Nebenwirkungen · Eviplera

Eviplera 200 mg/25 mg/245 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 22

HOS-214433 · Präparat HOS-155326

Frequency Adverse reaction Blood and lymphatic system disorders neutropenia1, decreased white blood cell count2, decreased haemoglobin2, decreased Common: platelet count2 Uncommon: anaemia1, 4 Immune system disorders Common: allergic reaction1 Uncommon: immune reactivation syndrome Metabolism and nutrition disorders increased total cholesterol (fasted)2, increased LDL-cholesterol (fasted)2, Very common: hypophosphataemia3, 5 Common: hypertriglyceridaemia1, 2, hyperglycaemia1, decreased appetite2 Uncommon: hypokalaemia3, 5 Rare: lactic acidosis3 Psychiatric disorders Very common: insomnia1, 2 Common: depression2, depressed mood2, sleep disorders2, abnormal dreams1, 2 Nervous system disorders Very common: headache1, 2, 3, dizziness1, 2, 3 Common: somnolence2 Gastrointestinal disorders Very common: increased pancreatic amylase2, vomiting1, 2, 3, diarrhoea1, 3, nausea1, 2, 3 elevated amylase including elevated pancreatic amylase1, elevated serum lipase1, 2, Common: abdominal pain1, 2, 3, abdominal discomfort2, abdominal distension3, dyspepsia1, flatulence3, dry mouth2 Uncommon: pancreatitis3 Hepatobiliary disorders Very common: increased transaminases (AST and/or ALT)1, 2, 3 Common: increased bilirubin1, 2 Rare: hepatitis3, hepatic steatosis3 Skin and subcutaneous tissue disorders Very common: rash1, 2, 3 vesiculobullous rash1, pustular rash1, urticaria1, skin discolouration (increased Common: pigmentation)1, 4, maculopapular rash1, pruritus1 Uncommon: angioedema1, 3, 6, severe skin reactions with systemic symptoms7 Musculoskeletal and connective tissue disorders Very common: elevated creatine kinase1 Common: bone mineral density decreased3 Uncommon: rhabdomyolysis3, 5, muscular weakness3, 5 osteomalacia (manifested as bone pain and infrequently contributing to fractures)3, 5, 8, Rare: myopathy3, 5 Renal and urinary disorders proximal renal tubulopathy including Fanconi syndrome3, increased creatinine3, Uncommon: proteinuria3 renal failure (acute and chronic)3, acute tubular necrosis3, nephritis (including acute Rare: interstitial nephritis)3, 8, nephrogenic diabetes insipidus3 General disorders and administration site conditions Very common: asthenia1, 3 Common: pain1, fatigue2 1 Adverse reaction identified for emtricitabine. 2 Adverse reaction identified for rilpivirine hydrochloride. 3 Adverse reaction identified for tenofovir disoproxil. 4 Anaemia was common and skin discolouration (increased pigmentation) was very common when emtricitabine was administered to paediatric patients (see section 4.8, Paediatric population).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Eviplera

Eviplera 200 mg/25 mg/245 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 22–23

HOS-214434 · Präparat HOS-155326

22 5 This adverse reaction may occur as a consequence of proximal renal tubulopathy. It is not considered to be causally associated with tenofovir disoproxil in the absence of this condition. 6 This was a rare adverse reaction for tenofovir disoproxil. It was also identified as an adverse reaction for emtricitabine through post-marketing surveillance but was not observed in randomised controlled clinical studies in adults or paediatric HIV clinical studies of emtricitabine. The frequency category of uncommon was estimated from a statistical calculation based on the total number of patients exposed to emtricitabine in these clinical studies (n = 1,563). 7 This adverse reaction was identified through post-marketing surveillance for Eviplera (fixed-dose combination) but not observed in randomised controlled clinical studies for Eviplera. The frequency category was estimated from a statistical calculation based on the total number of patients exposed to Eviplera or all of its components in randomised controlled clinical studies (n = 1,261). See section 4.8, Description of selected adverse reactions. 8 This adverse reaction was identified through post-marketing surveillance for tenofovir disoproxil but not observed in randomised controlled clinical studies or the expanded access program for tenofovir disoproxil. The frequency category was estimated from a statistical calculation based on the total number of patients exposed to tenofovir disoproxil in randomised controlled clinical studies and the expanded access program (n = 7,319).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Eviplera

Eviplera 200 mg/25 mg/245 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 23

HOS-214435 · Präparat HOS-155326

Laboratory abnormalities

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Nebenwirkungen · Eviplera

Eviplera 200 mg/25 mg/245 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 23

HOS-214436 · Präparat HOS-155326

Lipids At 96 weeks in the pooled Phase III C209 and C215 studies of treatment-naïve patients, in the rilpivirine arm the mean change from baseline in total cholesterol (fasted) was 5 mg/dL, in high-density lipoprotein (HDL)-cholesterol (fasted) 4 mg/dL, in low density lipoprotein (LDL)-cholesterol (fasted) 1 mg/dL, and in triglycerides (fasted) -7 mg/dL. At 48 weeks in Phase III study GS-US-264-0106 of virologically suppressed patients switching to Eviplera from a regimen containing a ritonavir-boosted PI, the mean change from baseline in total cholesterol (fasted) was -24 mg/dL, in HDL-cholesterol (fasted) -2 mg/dL, in LDL-cholesterol (fasted) -16 mg/dL, and in triglycerides (fasted) -64 mg/dL.

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Nebenwirkungen · Eviplera

Eviplera 200 mg/25 mg/245 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 23

HOS-214437 · Präparat HOS-155326

Description of selected adverse reactions

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Nebenwirkungen · Eviplera

Eviplera 200 mg/25 mg/245 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 23

HOS-214438 · Präparat HOS-155326

Renal impairment As Eviplera may cause renal damage, monitoring of renal function is recommended (see sections 4.4 and 4.8, Summary of the safety profile). Proximal renal tubulopathy generally resolved or improved after tenofovir disoproxil discontinuation. However, in some patients, declines in CrCl did not completely resolve despite tenofovir disoproxil discontinuation. Patients at risk of renal impairment (such as patients with baseline renal risk factors, advanced HIV disease, or patients receiving concomitant nephrotoxic medications) are at increased risk of experiencing incomplete recovery of renal function despite tenofovir disoproxil discontinuation (see section 4.4).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.